This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. ABSTRACT This is a multi-center, phase I type trial for children with recurrent or refractory medulloblastoma to select recommend a pharmacokinetic based daily dose of GDC-0449 for a subsequent Phase II trial to evaluate toxicity and to characterize the pharmacokinetics and biologics of the GDC-0449. I. HYPOTHESIS The proposed phase I type study of GDC 0449 will seek to describe the toxicities and pharmacokinetic characteristics of the drug in patients with recurrent or refractory medulloblastoma. Correlative studies on formalin fixed paraffin embedded tissue and snap frozen tissue (when available) will seek to select patients in whom the PTCH/SHH signaling pathway is activated. This information will be used in subsequent Phase II study so as to select a group of patients that are biologically optimal for treatment with this targeted therapy. II. SPECIFIC AIMS Primary Objectives: 1. To select, based on safety and pharmacokinetics, a daily dose of GDC0449 to recommend for a subsequent PBTC Phase II trial of children with recurrent or refractory medulloblastoma. Secondary Objectives: 1. To document and describe toxicities associated with GDC-0449 administered on a daily schedule. 2. To characterize the pharmacokinetics (plasma and cerebrospinal fluid) of GDC-0449 in children/adolescents with refractory medulloblastoma. 3. To document preliminary antitumor activity in patients with recurrent or refractory medulloblastoma treated with GDC-0449. 4. To document pathologic and genomic methods to identify CNS tumors with activation of the PTCH/SHH pathway.